上海交通大学倪俊研究小组实现基于iMARS的理性多酶结构设计。2025年1月23日，《细胞》杂志在线发表了这项成果。

研究人员开发了一个标准化框架，称为iMARS，用于通过整合高通量活性测试和结构分析，快速设计最佳的多酶结构。该方法展示了工业规模应用的潜力，iMARS设计的人工融合酶显著提高了白藜芦醇的生产（提高45.1倍）和树莓酮的生产（提高11.3倍），并增强了在补料批发酵中的黑色素氨酸合成。

此外，iMARS大大提高了多酶复合物在PET塑料降解和香草醛生物合成中的体外催化效率。作为一种可推广且灵活的分子层面策略，iMARS可以极大促进绿色化学、合成生物学和生物制造。

据介绍，具有空间邻近性的生物催化级联反应可以协调多步途径，形成代谢高速公路，从而提高整体催化效率。然而，空间组织对催化活性的影响尚不完全理解，且具有可预测性能的多酶结构工程尚未实现。

附：英文原文

Title: Rational multienzyme architecture design with iMARS

Author: Jiawei Wang, Xingyu Ouyang, Shiyu Meng, Bowen Zhao, Liangxu Liu, Chaofeng Li, Hengrun Li, Haotian Zheng, Yihan Liu, Ting Shi, Yi-Lei Zhao, Jun Ni

Issue&Volume: 2025-01-23

Abstract: Biocatalytic cascades with spatial proximity can orchestrate multistep pathways to form metabolic highways, which enhance the overall catalytic efficiency. However, the effect of spatial organization on catalytic activity is poorly understood, and multienzyme architectural engineering with predictable performance remains unrealized. Here, we developed a standardized framework, called iMARS, to rapidly design the optimal multienzyme architecture by integrating high-throughput activity tests and structural analysis. The approach showed potential for industrial-scale applications, with artificial fusion enzymes designed by iMARS significantly improving the production of resveratrol by 45.1-fold and raspberry ketone by 11.3-fold in vivo, as well as enhancing ergothioneine synthesis in fed-batch fermentation. In addition, iMARS greatly enhanced the in vitro catalytic efficiency of the multienzyme complexes for PET plastic depolymerization and vanillin biosynthesis. As a generalizable and flexible strategy at molecular level, iMARS could greatly facilitate green chemistry, synthetic biology, and biomanufacturing.

DOI: 10.1016/j.cell.2024.12.029

Source: https://www.cell.com/cell/abstract/S0092-8674(24)01471-5